Frontiers

What the Bacteria Saw

By using Lyme disease bacteria to research evolution, Assistant Professor of Biology Dustin Brisson is advancing both science and medicine.
February 2014

“We do things from the bacteria’s point of view,” says Assistant Professor of Biology Dustin Brisson. “They have their own ecology, evolution, and natural history, and you have to treat them as such, not just as an infectious agent.”

Brisson uses pathogens—particularly Borrelia burgdorferi, the bacterium that causes Lyme disease—to study basic questions of biology. To outpace the immune systems of their hosts, B. burgdorferi and other bacteria must be very adaptable. This makes them a good system to study fundamental questions in ecology—interactions that affect distribution and abundance—and evolution—changes in the frequency of variants due to neutral or selected processes.

Along the way, his use of B. burgdorferi has also let his work directly impact medical knowledge about Lyme disease, giving it the potential to change the disease’s detection and treatment. Brisson and his colleagues just published a paper based on five years of field research that showed a bait-delivered vaccine successfully disrupted the transmission path between animal hosts like mice and shrews and the ticks, and lowered the population of infected ticks. “It shows it is possible to lower human Lyme disease risk, and it’s a short step to make this practical,” he says.

Brisson is also working with Professor of Physics and Astronomy A.T. Charlie Johnson to attach Lyme disease antibodies to carbon nanotubes. These nanotubes—rolled-up lattices of carbon atoms—are highly conductive and sensitive to electrical charge. By attaching different biological structures to the exteriors of the nanotubes, they can function as very sensitive and specific biosensors.

Currently, tests for Lyme disease check samples of patients’ blood for the antibodies that are created in response to B. burgdorferi. These antibodies, however, take weeks to form in the body and persist after the infection is gone. The Penn team realized they could turn the equation around by introducing the antibodies into a patient’s blood sample to see if the bacterium is present; if it is, the antibody will bind to it. The detector worked with a sensitivity that Brisson says is more than sufficient to detect the Lyme disease bacterium in the blood of recently-infected patients.

Because he’s looking at basic biological questions, much of Brisson’s research can translate to other diseases, as well as telling us more about evolution and ecology in general. He recently published a paper which for the first time gave clear evidence that evolution can select for evolvability—genes that can easily evolve.

He’s also working on a mathematical model that predicts the frequency of each B. burgdorferi genotype from empirical data on the density of host species and the rate each genotype is transmitted from hosts to ticks, allowing him predict the risk of human Lyme disease in locales around the northeastern United States.

But, he says, “The nice thing about prediction is you’re always wrong. When you figure out where you’re wrong and why you’re wrong, it tells you a lot about biology and function. You might find something that wasn’t even on the radar screen before. Who knew? And now we can investigate it.”